The present invention relates to a process for preparing N-carbamoyl-D-(2-thienyl or 3-thienyl)glycine which can be readily converted into D-(2-thienyl or 3-thienyl)glycine, and more particularly to a process for preparing N-carbamoyl-D-(2-thienyl or 3-thienyl)glycine by biochemically hydrolyzing 5-(2-thienyl or 3-thienyl)hydantoin by employing intracellular enzymes of microorganisms.
The present inventors already found that N-carbamoyl-D-(phenyl or substituted phenyl)glycines can be prepared by subjecting 5-(phenyl or substituted phenyl)hydantoins to the action of microbial enzymes (U.S. Pat. No. 4,094,741), and also that N-carbamoyl-D-.alpha.-amino acids can be prepared from 5-substituted hydantoins corresponding to natural amino acids or their substituted derivatives in the same manner as above (U.S. patent application Ser. No. 862,853).
It is well known that D-thienylglycines are an available intermediate for the preparation of antibiotics such as semi-synthetic penicillins and semi-synthetic cephalorsporins. As a process for preparing D-thienylglycine, there is reported in Journal of the Chemical Society of Japan, Vol. 82, No. 12, 1688-1691 (1961) a process in which DL-thienylglycine is prepared from thiophene aldehyde by Streker method and is subjected to N-chloroacetylation, and after subjecting only the L-form to the dechloroacetylation by employing acylase extracted from kidney of a pig the residual N-chloroacetyl-D-thienylglycine is hydrolyzed. A process is also known in which acylase obtained from microorganisms is employed in the optical resolution of N-chloroacetyl-DL-thienylglycine, as disclosed in Japanese Unexamined Patent Publication No. 6489/1978. In U.S. Pat. No. 3,198,804, there is disclosed a process in which DL-thienylglycine is produced by hydrolyzing 5-thienylhydantoin synthesized from thiophene aldehyde and is then subjected to optical resolution by employing d-10-camphorsulfonic acid. However, these processes require the use of the expensive acylase or require steps of recovering and racemizing a residual unnecessary optical isomer.